No abstract

Camelids have a special type of antibodies, known as heavy chain antibodies (HCAbs), that are devoid of classical antibody light chains. Relative to classical antibodies, camelid HCAbs (cAbs) have comparable immunogenicity, antigen recognition diversity and binding affinities, higher stability and solubility, and better manufacturability, making them promising candidates for alternate therapeutic scaffolds. Rational engineering of cAbs to improve therapeutic function requires knowledge of the differences of sequence and structural features between cAbs and classical antibodies. Here, amino acid sequences of 27 cAb variable regions (VHH) were aligned with the respective regions of 54 classical antibodies to detect amino acid differences, enabling automatic identification of cAb VHH complementarity determining regions (CDRs). CDR analysis revealed that the H1 often (and sometimes the H2) adopts diverse conformations not classifiable by established canonical rules. Also, while the cAb H3 is much longer than classical H3 loops, it often contains common structural motifs and sometimes a disulfide bond to the H1. Leveraging these observations, we created a Monte Carlo based cAb VHH structural modeling tool, where the CDR H1 and H2 loops exhibited a median root-mean-square-deviation (rmsd) to native of 3.1 and 1.5 Å respectively. The protocol generated 8-12, 14-16 and 16-24 residue H3 loops with a median rmsd to native of 5.7, 4.5 and 6.8 Å respectively. The large deviation of the predicted loops underscores the challenge in modeling such long loops. cAb VHH homology models can provide structural insights into interaction mechanisms to enable development of novel antibodies for therapeutic and biotechnological use.

We present here the first curated collection of wild and cultivated African rice species. For that, we designed specific SNPs and were able to structure these very low diverse species. Oryza glaberrima, the cultivated African rice, is endemic from Africa. This species and its direct ancestor, O. barthii, are valuable tool for improvement of Asian rice O. sativa in terms of abiotic and biotic stress resistance. However, only a few limited studies about the genetic diversity of these species were performed. In the present paper, and for the first time at such extend, we genotyped 279 O. glaberrima, selected both for their impact in current breeding and for their geographical distribution, and 101 O. barthii, chosen based on their geographic origin, using a set of 235 SNPs specifically designed for African rice diversity. Using those data, we were able to structure the individuals from our sample in three populations for O. barthii, related to geography, and two populations in O. glaberrima; these two last populations cannot be linked however to any currently phenotyped trait. Moreover, we were also able to identify misclassification in O. glaberrima as well as in O. barthii and identified new form of O. sativa from the set of African varieties.